True uterus didelphys in she-camel: a case report and review of literature.

Background: Uterus didelphys is a rare congenital anomaly of the female reproductive tract characterized by a divided uterine cervix and body. It occurs due to abnormal development of the paramesonephric (Müllerian) duct. Different forms of uterus didelphys have been reported in several animal species, including bovine, equine, ewe, goat, swine, and bitch. However, there is no previous report that has documented a completely divided female genital tract in she-camel. Moreover, there is a lack of literature regarding this anomaly in animals. Therefore, the present study reports, for the first time, a rare case of a completely divided female genital tract in a she-camel. In addition, the existing relevant literature on uterus didelphys in different animal species is reviewed. Case presentation: A female reproductive tract of she-camel, approximately 10 years old, with a history of previous successful pregnancy, was brought to the anatomy department following the slaughtering of the animal. Initial examination revealed a normal reproductive tract consisting of two ovaries, two fallopian tubes, a uterus, and a vagina. A closer examination revealed a completely divided vagina, with an external os opened into each part of the vagina, as well as a divided uterine body and cervix. Intrauterine infusion of saline through one external os confirmed complete separation of uterine body and cervix. Conclusion: To the authors' knowledge, this is the first reported case of a completely divided female genital tract in a she-camel. This review summarizes the previous reports about uterus didelphys in farm animals.

Unicornuate uterus with a rudimentary non-communicating cavitary horn in association with VACTERL association: a rare case report.

Mullerian anomalies are malformations that affect the embryological development of paramesonephric ducts and are associated with multiple urogenital defects due to shared embryology, including VACTERL association, which coexists in about one-third of these patients. We report a rare case of a unicornuate noncommunicating horn uterus with a rudimentary second horn in a known case of VACTERL association in a 16-year-old girl.

Implication of androgen receptor gene dysfunction in human Müllerian duct anomalies.

BACKGROUND: Müllerian duct anomalies (MDAs) are congenital developmental disorders exhibiting as a variety of malformations of female reproductive tract. The identified etiology of MDAs is limited. The present study aimed to unravel the underlying genetic causes of MDAs. METHODS: Rare variants in androgen receptor (AR) were called from the cohort consists of patients with MDAs and underwent whole exome sequencing (WES) at Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing, China. Sanger sequencing was used to confirm the causative genetic mutations. In silico analysis were used to classify the pathogenicity of each variant. Molecular modeling and simulations were conducted to investigate the conformational changes between the wild-type (WT) and mutant proteins. RESULTS: A total of 3 rare heterozygous variants in AR from the MDAs cohort in our institution were identified, with unknown effects. All variants were missense mutations, including c.173A > T, c.558C > A and c.1208C > T, and were absent or rare in East Asian populations in Genome Aggregation Database and the Exome Aggregation Consortium Database. According to the American College of Medical Genetics and Genomics guidelines, c.1208C > T variant was classified as likely pathogenic, while the other two were variants of uncertain significance. During molecular dynamics simulations, WT and mutant proteins all reached stable status according to root-mean-square variance. Values of radius of gyration showed that Q58L and S186R protein would be more compact than WT, while the structure of A403V became looser. Despite, in comparison with WT, the number of hydrogen bonds increased in Q58L, while decreased in the other two variants. Furthermore, the solvent-accessible surface area diminished in Q58L and A403V while enlarged in S186R proteins, when compared with WT. CONCLUSIONS: To our knowledge, this is the first report regarding the association of AR mutation and MDAs. The identification of these variants, predicted to damage the structure and function of AR protein, not only expanded the mutational spectrum of causative genes of MDAs, but provide novel molecular genetic reference for future studies.

Endometrial Cancer in a Patient With Didelphys Uterus and a History of Renal Cancer: A Case Report and Literature Review.

Müllerian duct anomalies (MDAs) concurrent with endometrial cancer are exceptionally rare, with only a few documented cases. Here, we present a case of endometrial cancer in both horns of a didelphys uterus in a 54-year-old woman with a history of renal cancer, who underwent left radical nephrectomy and left salpingo-oophorectomy. The patient sought medical evaluation due to postmenopausal vaginal bleeding. Hysteroscopy with dilation and curettage revealed the presence of two cervixes and two endometrial cavities, with pathology results indicating endometrioid adenocarcinoma (G1). Preoperative MRI staging confirmed the diagnosis of a double cervix and uterus. Subsequently, an open abdominal hysterectomy and a right salpingo-oophorectomy were performed, revealing a didelphys uterus (International Federation of Gynaecology and Obstetrics 2018, stage IA). This manuscript aims to explore the potential correlation between renal and endometrial malignancies in the presence of MDAs.

Müllerian Duct Anomalies and Anti-Müllerian Hormone Levels in Women With Polycystic Ovary Syndrome.

BACKGROUND: Significant associations between the presence of polycystic ovary syndrome (PCOS) and uterine anomalies have been reported. It is unclear whether high anti-Müllerian hormone (AMH) levels coexist with the development of uterine malformations in women with PCOS. This study sought to investigate the association between Müllerian duct anomalies and anti-Müllerian hormone (AMH) levels in women with PCOS. METHODS: In this retrospective cohort study, the records of 1,391 women with PCOS were analyzed. The cohort was divided into a low-AMH group (n = 700) and a high-AMH group (n = 691), based on an AMH cutoff value of 8.45 ng/ml. Müllerian duct anomalies were classified into four subtypes based on three-dimensional ultrasonography: septate uterus, bicornuate uterus, uterus didelphys, unicornuate uterus, and arcuate uterus. The primary outcome was the overall incidence of Müllerian duct anomalies. The secondary outcome was the prevalence of the abovementioned specific types of Müllerian duct anomalies. The prevalence of Müllerian duct anomalies was analyzed using the chi-squared test or Fisher's exact test. RESULTS: Among the patients with PCOS, the prevalence of unicornuate uterus anomalies was higher in the high-AMH group than in the low-AMH group (1.0% vs. 0.1%, P = 0.04). No statistically significant difference in the overall incidence of uterine malformations was found between the two AMH groups (4.3% vs. 5.7%, P = 0.22). CONCLUSIONS: Our study confirmed a higher prevalence of unicornuate uterus in PCOS women with high AMH levels. Clinicians might decide to investigate the possibility of a unicornuate uterus in PCOS women with high AMH levels.

Aggressive Cervical Dilation Exploits Potential Weakness in the Septum of Duplicated Cervix during Hysteroscopic Cervix-preserving Metroplasty of Complete Septate Uterus: A Cohort Study.

STUDY OBJECTIVE: To evaluate whether aggressive cervical dilation is effective for creating the initial perforation between noncommunicating cavities of the complete septate uterus (CSU), which serves as the first step of hysteroscopic cervix-preserving metroplasty (CPM). DESIGN: A retrospective cohort. SETTING: A tertiary referral center. PATIENTS: Fifty-three patients with CSU were diagnosed using vaginal examinations, combined two- and three-dimensional vaginal ultrasounds, and office-based hysteroscopies. INTERVENTIONS: Patients who had received hysteroscopic CPM with the initial perforation created by aggressive cervical dilation or by the traditional method of bougie-guided incisions were compared. MEASUREMENTS AND MAIN RESULTS: Of the 53 patients with CSU, 44 patients received hysteroscopic CPM that required the creation of a perforation. Patients who received aggressive cervical dilation for creation of the perforation had nonsignificantly shorter surgical times (33.5 minutes, 95% confidence interval [CI], 28.4-38.6 vs 48.7 minutes, 95% CI, 28.2-71.3, p = .099), used significantly lower volumes of distending media (3.6 liters, 95% CI, 3.1-4.1 vs 6.8 liters, 95% CI, 4.2-9.3, p <.001), and had higher success rates (84.4%, 95% CI, 67.2-94.7 vs 50.0%, 95% CI, 21.1-78.9, p = .019). The sites of perforation all occurred on the endocervical septum and were generally fibrous and avascular. CONCLUSION: We present a novel, effective method for creating the initial perforation in hysteroscopic CPM. The success may be because of the existence of a potential weakness in the septum of the duplicated cervix, which spontaneously tears upon aggressive mechanical dilation. The method forgoes the risks associated with sharp incisions based on potentially unreliable cues and may greatly simplify the procedure.

An atypical Müllerian duct anomaly: Duplicated cervices and vaginas with a single uterine cavity.

Müllerian duct anomalies include a wide variety of developmental abnormalities involving the female reproductive system, many of which are not adequately represented by the current classification system used in the United States. Diagnosis can be made with imaging, but initial evaluation first requires a thorough physical exam. A 19-year-old female received a pelvic MRI for evaluation of a Müllerian duct anomaly following an abnormal pelvic exam. Imaging demonstrated a single uterine cavity which divides into 2 distinct cervices and vaginas. The patient received a hysteroscopic resection of her vaginal septum. This type of anomaly is extremely rare and associated clinical outcomes of potential infertility or complications with vaginal delivery are uncertain. Use of a more comprehensive classification system for Müllerian duct anomalies may assist with identification and research of such rare subtypes.

A rare case report of uterine didelphys, in which one uterus carried a pregnancy while the other prolapsed, with a successful pregnancy outcome resulting in an alive-term delivery.

Uterine didelphys is a rare congenital anomaly of the female reproductive organs, designated by the presence of the uterus as a pair of organs. This occurs as a result of the failure of the embryonic fusion of Müllerian ducts. Women with this abnormality have a paired uterus with two cervices and usually a double vagina. The chance of having a pregnancy in one of the pairs along with prolapse of the other is very low in a didelphic uterus. To the best of the author's knowledge, only one case of such an event has been reported so far. In this case report, we are reporting on a 28-year-old gravida four para three (all are vaginal deliveries, 2 are alive, healthy, and term deliveries without any compilation; 1 is an early neonatal death delivered at 8 months) woman who presented to our hospital with a complaint of a protruding mass per vagina for 14 days in the presence of pregnancy. After she was evaluated and investigated, she was diagnosed with pelvic organ prolapse and late-preterm pregnancy. The prolapse reduced gradually as the gestational age advanced. Cesarean section was done at the gestational age of 38 weeks plus 2 days for the indication of infected pelvic organ prolapse in labor, with the outcome of a 3000 gram male alive neonate. Intraoperatively, there was uterine didelphys, one uterus holding the pregnancy while the other was prolapsing.

A Common Path: Magnetic Resonance Imaging of Müllerian and Wolffian Duct Anomalies.

PURPOSE OF REVIEW: This review summarizes the pathway of Mullerian and Wolffian duct development, anomalies that result from disruptions to this pathway, and the characteristics on advanced imaging that identify them. RECENT FINDINGS: In-office evaluation for reproductive anomalies is usually inadequate for the diagnosis of congenital reproductive anomalies. Magnetic resonance imaging (MRI) has usurped invasive diagnostic methods including laparoscopy, hysteroscopy, and vasography as the new gold standard. Because of its superior soft-tissue delineation and the availability of advanced functional sequences, MRI offers a sophisticated method of distinguishing reproductive anomalies from one another, characterizing the degree of defect severity, and evaluating for concomitant urogenital anomalies non-invasively and without radiation exposure to the patient. Congenital anomalies of the Mullerian and Wolffian duct can be incredibly nuanced, requiring prompt and accurate diagnosis for management of infertility. Definitive diagnosis should be made early with MRI.

MRI Evaluation of Mullerian Duct Anomalies: Practical Classification by the New ASRM System.

Objective: To describe variable mullerian duct anomalies using magnetic resonance imaging (MRI) and to classify these anomalies according to the available classification systems, namely the American Fertility Society (AFS) system, the European Society of Human Reproduction and Embryology (ESHRE) system, and the new American Society for Reproductive Medicine (ASRM) system. Design: Retrospective chart review. Subjects: The pelvic MRI studies and the clinical records of 64 females with mullerian congenital anomalies were retrospectively reviewed between January 2010 and December 2021. The mean age was 22 years (age range 2-63 years). Main Outcome Measures: Detailed imaging findings were recorded, and the resulting mullerian anomalies were then classified according to the three classification systems of interest. Results: Variable mullerian anomalies were found among patients with multiple frequencies. Mullerian agenesis and hypoplasia were found in 12 patients (19%) and 16 patients (25%), respectively. Uterus didelphys was found in 5 patients (8%). Twelve (19%) patients had septate uterus, while 8 (12.5%) had a bicornuate anomaly. Unicornuate uterus was present in 7 patients (11%). Isolated vaginal anomaly was diagnosed in 4 patients (6%). Renal/urinary tract imaging was available for 27 (42%) patients, and accompanying urinary tract anomalies were noted in 10 of them (37%). Few ovarian and other extra-renal anomalies were observed. Conclusion: MRI could efficiently delineate the mullerian anomalies regardless of their complexity. Most of these anomalies were more efficaciously categorized by the ESHRE and the new ASRM systems, compared to the originally widely used AFS system. The new ASRM classification was found to be more practical as it is a modification of the original AFS system, using drawings with clear descriptions instead of symbols. This is particularly helpful in the radiological era, saving time and effort.

Preoperative MRI presentations of Herlyn-Werner-Wunderlich syndrome.

Herlyn-Werner-Wunderlich (HWW) syndrome is a rare complex female urogenital anomaly, with diverse anatomical presentations. Due to obstruction, most patients with HWW syndrome need to be addressed surgically. The treatment strategy should be tailored to the different anatomical variants of each patient. Therefore, a detailed and comprehensive preoperative evaluation is needed. In this review, we describe the embryology and clinical manifestations of HWW syndrome and discuss and illustrate its diverse preoperative magnetic resonance imaging presentations to guide clinical treatment.

High-grade cervical dysplasia in a woman with uterine didelphys: A case report.

The combination of lower genital tract carcinomas with genitourinary malformations is a rare occurrence. The purpose of this report is to describe the case of high-grade cervical dysplasia of the left cervix of a woman with a uterine didelphys and additional urinary tract malformations.

A rare variant of obstructed hemivagina and ipsilateral renal agenesis and its improvement of classification.

Obstructed hemivagina and ipsilateral renal agenesis (OHVIRA) is a rare congenital malformation of the female reproductive organs, including uterine dysplasia, blind hemivagina, and ipsilateral renal dysplasia. It has a serious impact on patients' quality of life and fertility. We report a rare case of OHVIRA with a complete septate uterus, ectopic dysplasia of the left kidney, left ectopic ureter, and three oblique vaginal septa. The dysplastic left kidney and the ectopic ureter were removed during laparoscopy. In addition, the two layers of vaginal septa, which were ignored in the past 10 years, were removed by hysteroscopy. As the detection rate of OHVIRA has gradually increased, manifestations that previous classification systems could not recapitulate have emerged. By retrieving the relevant cases, we have tried to propose a new classification system, which would allow clinicians to have a complete understanding of the manifestations of OHVIRA and would be helpful in the treatment of patients.

A Unique Case of Unicornuate Uterus With a Non-communicating Rudimentary Horn and Hematometra.

Congenital uterine anomalies are a rare type of malformation involving female genitalia caused by abnormal development of the Mullerian duct system. Patients having an obstructive type of uterine anomalies are very much likely to develop obstetric and gynecological complications usually at the age of menarche or later in the course of life. In this case report, we present a case of a young female patient having severe dysmenorrhea which is caused by obstructive hematometra in the rudimentary horn which is not communicating with the uterine cavity. Ultrasonography (USG) was used to make a differential diagnosis of a probable congenital abnormality, which was subsequently validated by magnetic resonance imaging (MRI), which revealed a uterine cavity having a single cornu on the left side seen to be connecting with the cervix and a dilated rudimentary horn on the right side. The patient underwent the excision of the rudimentary horn laparoscopically. This case emphasizes the importance of identifying patients having anomalies involving the uterus to provide appropriate treatment to the patient and to prevent adverse outcomes for her reproductive potential.

Studying Müllerian duct anomalies - from cataloguing phenotypes to discovering causation.

Müllerian duct anomalies (MDAs) are developmental disorders of the Müllerian duct, the embryonic anlage of most of the female reproductive tract. The prevalence of MDAs is 6.7% in the general female population and 16.7% in women who exhibit recurrent miscarriages. Individuals affected by these anomalies suffer from high rates of infertility, first-trimester pregnancy losses, premature labour, placental retention, foetal growth retardation and foetal malpresentations. The aetiology of MDAs is complex and heterogeneous, displaying a range of clinical pictures that generally lack a direct genotype-phenotype correlation. De novo and familial cases sharing the same genomic lesions have been reported. The familial cases follow an autosomal-dominant inheritance, with reduced penetrance and variable expressivity. Furthermore, few genetic factors and molecular pathways underpinning Müllerian development and dysregulations causing MDAs have been identified. The current knowledge in this field predominantly derives from loss-of-function experiments in mouse and chicken models, as well as from human genetic association studies using traditional approaches, such as microarrays and Sanger sequencing, limiting the discovery of causal factors to few genetic entities from the coding genome. In this Review, we summarise the current state of the field, discuss limitations in the number of studies and patient samples that have stalled progress, and review how the development of new technologies provides a unique opportunity to overcome these limitations. Furthermore, we discuss how these new technologies can improve functional validation of potential causative alterations in MDAs.

Diagnosis and Surgical Treatment of Uterine Isthmus Atresia: A Case Report and Review of the Literature.

Uterine isthmus atresia is a rare Müllerian duct anomaly occasionally diagnosed in adolescents with primary amenorrhea and cyclic abdominal pain. A case is presented of a 14-year-old female with monthly cyclic lower abdominal pain of a 2-year duration. Magnetic resonance imaging and 3-dimensional ultrasound showed separation of a 10-mm fibrotic tissue between the cervical canal and the endometrial cavity. In an attempt to preserve reproductive ability, an end-to-end anastomosis was laparoscopically performed between the cervical canal and uterine cavity. A platinol stent (WallFlex Biliary RX; Boston Scientific, Boston, MA) was placed by hysteroscopy to avoid stenosis after surgery. Laparoscopic end-to-end anastomosis is proposed to treat congenital uterine isthmus atresia.

One patient with two uteri and two pregnancies - a rare case of twins in a patient with uterus didelphys.

We report an extraordinary case of double pregnancy in patient with uterus didelphys. This anatomic anomaly originates from the lack of fusion of the paired Mullerian ducts during embryological development with 0.3% prevalence in the population. The patient presented to our department with initial diagnosis which was confirmed during ultrasound examination at 12 weeks - uterus didelphys with dichorionic diamniotic twin gestation. Further ultrasound scans were performed every 4 weeks and revealed small for gestational age fetuses. Due to the uterine malformation and the history of cesarean section, the patient was qualified for an elective cesarean section at 36 weeks of gestation - two premature neonates were delivered in good general conditions.

Uterine cervical cancer associated with obstructed hemivagina and ipsilateral renal agenesis (OHVIRA) syndrome: A case report and review of the literature.

•Cervical cancer occurring in patients with OHVIRA syndrome is very rare.•This case reports on HPV-negative adenocarcinoma located in the nonvisible cervix.•Colposcopy and imaging are essential for cervical cancer with uterine malformation.•In OHVIRA syndrome, cervical malignancies may be overlooked.

Niche role of MRI in the evaluation of female infertility.

Infertility is a major social and clinical problem affecting 13-15% of couples worldwide. The pelvic causes of female infertility are categorized as ovarian disorders, tubal, peritubal disorders, and uterine disorders. Appropriate selection of an imaging modality is essential to accurately diagnose the aetiology of infertlity, since the imaging diagnosis directs the appropriate treatment to be instituted. Imaging evaluation begins with hystero- salpingography (HSG), to evaluate fallopian tube patency. Uterine filling defects and contour abnormalities may be discovered at HSG but usually require further characterization with pelvic ultrasound (US), sono-hysterography (syn: hystero-sonography/saline infusion sonography) or pelvic magnetic resonance imaging (MRI), when US remains inconclusive. The major limitation of hysterographic US, is its inability to visualize extraluminal pathologies, which are better evaluated by pelvic US and MRI. Although pelvic US is a valuable modality in diagnosing entities comprising the garden variety, however, extensive pelvic inflammatory disease, complex tubo-ovarian pathologies, deep-seated endometriosis deposits with its related complications, Mulllerian duct anomalies, uterine synechiae and adenomyosis, often remain unresolved by both transabdominal and transvaginal US. Thus, MRI comes to the rescue and has a niche role in resolving complex adnexal masses, endometriosis, and Mullerian duct anomalies with greater ease. This is a review, based on the authors' experience at tertiary care teaching hospitals and aims to provide an imaging approach towards the abnormalities which are not definitively diagnosed by ultrasound alone.

Aberrant DNA methylation in the PAX2 promoter is associated with Müllerian duct anomalies.

PURPOSE: Abnormalities during Müllerian duct and female reproductive tract formation during embryonic development result in Müllerian duct anomalies (MDA). Previous studies have identified a role for mutations in related genes and DNA copy number variation (CNV). However, the correlation between gene methylation and MDA remains to be understood. METHODS: Endometrial tissues were collected from patients with septate (n = 23) or normal uterus (n = 28). We detected the methylation status of CpG sites and mRNA levels of nine candidate genes, including HOXA10, EMX2, TP63, ITGB3, PAX2, LHX1, GSC, WNT4, and H19, using MethyTarget and quantitative real-time polynucleotide chain reaction (qRT-PCR), respectively RESULTS: Compared with healthy controls, we detected three hypomethylated CpG sites (P < 0.05) and increased mRNA levels of PAX2 (P < 0.05) in individuals with MDA. HOXA10, EMX2, TP63, ITGB3, LHX1, and GSC had 1, 1, 2, 1, 5, and 2 differentially methylated CpG sites (P < 0.05), respectively, but there were no significant differences in their mRNA levels (P > 0.05). WNT4 and H19 did not show differences in methylation (P > 0.05) and mRNA levels (P > 0.05). CONCLUSIONS: Aberrant DNA methylation within the promoter of PAX2 may contribute to the development of MDA by regulating its gene expression. However, the methylation status of HOXA10, EMX2, TP63, ITGB3, LHX1, GSC, WNT4, and H19, may not contribute to the development of MDA.